tbuckley/cabot-search huggingface dataset:
MEDB-13. Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol
Authors: Marie-Sophie Merlin, Emmanuelle Schmitt, Malika Mezloy-Destracque, Christelle Dufour, Laurent Riffaud, Chloé Puiseux, Emilie De Carli, Damien Bodet, Céline Icher, François Doz, Cécile Faure-Conter, Anne Pagnier, Claire Pluchart, Sandrine Thouvenin-Doulet, Julien Lejeune, Phi-Linh Nguyen Thi-Lambert, Pascal Chastagner
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: HIT-SKK protocol is used for the treatment of low risk medulloblastomas in young children with the aim of eliminating cranial irradiation and its long-term side effects, in particular neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders.The objectives are to describe the risk factors and the course of LE, and to investigate its impact on long-term neurocognitive and behavioural outcome. METHODS: A French retrospective, multicenter study including 35 children under 5 years of age, treated between 2009 and 2017, with a median follow up of 72 months. All follow-up MRIs including assessment of the severity of the LE (Fazekas and CTCAE grading) and all NP evaluations were centrally rewieved. RESULTS: 25/34 evaluable patients presented a LE during follow up, in a median delay of 2 months (1 - 17 months) after the start of chemotherapy. Grade 2 and 3 abnormalities were correlated with higher cumulative dose of ITV -MTX (p=0,01). Full Scale IQ (FSIQ) and Wechsler indexes were in the average or low average of the reference population. FSIQ was deficient in 7/20 evaluable patients. Processing speed (PSI) was the most frequently impaired neurocognitive domain: 9/20 patients with borderline or very low score, all having received a significantly higher cumulative dose of ITV-MTX (p=0,04). A decrease in overall NP scores was observed in patients for whom grade 2 or 3 LE persisted at the end of follow-up with an average FSIQ estimated at 82.1 (SD 16.9) versus 94.2 (SD 20.6). This decrease was significant for PSI (p=0,049). LE and neurocognitive impairments were not correlated with a younger age at diagnosis. CONCLUSION: This study confirmed the responsibility of MTX, and in particular ITV-MTX therapy in the onset and, most often, persistence of LE and its association with neurocognitive disorders.
RONC-04. Relationship between proton therapy and the development of the limbic system in pediatric posterior fossa tumors
Authors: Anne E M Leenders, Bruno M Brito de Robalo, Geert O R Janssens, Eelco W Hoving, Maarten H Lequin, Marita H Partanen
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Pediatric brain tumor survivors may develop neuropsychological impairments after treatment. The first months after treatment could be a crucial time-window where the development of the brain may be affected by different types of treatments. For example, deficits in memory and learning related to hippocampal damage have resulted in radiotherapy dose constraints to the hippocampus. However, other limbic system substructures, important for cognition or behavior, may suffer from collateral doses. Therefore, we investigated the early effect of treatment on limbic structure volume. We hypothesized that radiotherapy (vs. no radiotherapy) would contribute to a decrease in volume of the limbic structures. METHODS AND MATERIALS: Thirty-eight patients with a tumor in the posterior fossa region (medulloblastoma n=12; pilocytic astrocytoma n=24; other=2) who were diagnosed between June 2018 and September 2020 and were alive ≥1 year diagnosis were included. Patients receiving neurosurgery only (n=26) were compared to patients treated with neurosurgery, proton therapy and chemotherapy (n=12). Limbic structures were automatically segmented in 111 MRI scans. These structures were amygdala, hippocampus (CA1+CA2/3), subiculum, dentate gyrus, parahippocampal gyrus, fornix, mammillary bodies, nucleus accumbens and thalamo-anteroventral nucleus of thalamus. RESULTS: Analyses revealed a significant negative effect of time on the amygdala (p&amp;lt;0.01), hippocampus (CA1) (p&amp;lt;0.001), and dentate gyrus (p&amp;lt;0.01). This indicates that these structures decreased in volume within the first year after diagnosis, independent of radiation treatment. Furthermore, an interaction effect was found between time and radiation in the subiculum (p=0.02) and fornix (p=0.052). CONCLUSION: These results indicate that the volumetric decline were stronger for the patients that received proton radiation. Future comparisons will test how results relate to the volumes in healthy children of the same age. Also, we will investigate whether this abnormal development is associated to the radiation dose and how it relates to the neuropsychological outcomes of the child over time.
Imaging intensity after surgery for clear cell renal cell carcinoma
Authors: A. Martini, F. Belladelli, D. Cignoli, G. Rosiello, G. Fallara, G. Basile, L. Nocera, G. Colandrea, D. Canibus, C. Re, G. Musso, F. Cei, F. De Cobelli, G. Brembilla, A. Briganti, R. Bertini, A. Necchi, D. Raggi, F. Montorsi, A. Salonia, A. Larcher, U. Capitanio
Journal: European Urology (2022)
A drop-in gamma probe for sentinel lymph node dissection in prostate cancer: Interim results from a multicentre clinical trial
Authors: C. Solà Marqués, J.M. Abascal Junquera, L. Cecchini, J.C. Walz, W. Everaers, K. Goffin, M.R. Grootendorst, F. Oldfield, A. Mestre Fusco, S. Vidal-Sicart, L. Fumado
Journal: European Urology (2022)
Prophylactic tranexamic acid in patients with hematologic malignancy: a placebo-controlled, randomized clinical trial
Authors: Terry B. Gernsheimer, Siobhan P. Brown, Darrell J. Triulzi, Nigel S. Key, Nahed El Kassar, Heather Herren, Jacqueline N. Poston, Michael Boyiadzis, Brandi N. Reeves, Subodh Selukar, Monica B. Pagano, Scott Emerson, Susanne May
Journal: Blood (2022)

Evidence of the effectiveness of prophylactic use of tranexamic acid (TXA) in thrombocytopenia is lacking. To determine whether TXA safely reduces bleeding incidence in patients undergoing treatment for hematologic malignancies, a randomized, double-blind clinical trial was conducted from June 2016 through June 2020. Of 3120 screened adults, 356 patients were eligible and enrolled, and 337 patients (mean age, 53.9; 141 [41.8%] women), randomized to 1300 mg TXA orally or 1000 mg TXA through IV (n = 168) vs placebo (n = 169) thrice daily for maximum 30 days. Three hundred thirty patients were activated when their platelet counts fell below 30 000 per µL; 279 (83%) had complete outcome ascertainment. World Health Organization (WHO) grade ≥2 bleeding was observed in the 30 days following activation in 50.3% (73/145) and 54.2% (78/144) of patients in the TXA and placebo groups, with an adjusted odds ratio of 0.83 (95% confidence interval [CI], 0.50-1.34; P = .44). There was no statistically significant difference in the mean number of platelet transfusions (mean difference, 0.1; 95% CI, -1.9 to 2.0), mean days alive without grade ≥2 bleeding (mean difference, 0.8; 95% CI, -0.4 to 2.0), thrombotic events (6/163 [3.7%] TXA, 9/163 [5.5%] placebo), or deaths due to serious bleeding. Most common adverse events were: diarrhea (116/164 [70.7%] TXA and 114/163 [69.9%] placebo); febrile neutropenia (111/164 [67.7%] TXA, 105/163 [64.4%] placebo); fatigue (106/164 [64.6%] TXA, 109/163 [66.9%] placebo); and nausea (104/164 [63.4%] TXA, 97/163 [59.5%] placebo). Among patients with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation, prophylactic treatment with TXA compared with placebo did not significantly reduce the risk of WHO grade ≥2 bleeding.
Understanding disparities in research publications in high-impact factor journals by cancer site.
Authors: Nikita Sinha, Amanda McDonald, Danika Barry, Emma Longley Barber
Journal: Journal of Clinical Oncology (2022)

e13626 Background: Prior studies have shown disparities in funding allocation for gynecologic cancers after accounting for their mortality, incidence, and person-years of life lost. Whether disparities exist in high impact factor journals is unknown. The purpose of this study is to analyze research publication trends in high impact factor journals comparing gynecologic cancers to other cancers from 2000 to 2018. Methods: Abstracts from the top 55 impact factor journals, as measured by Clarivate, from 2000 to 2018 were extracted from PubMed. We developed an algorithm to search the title of the abstract to determine whether the abstract was about cancer and identify the cancer type. The algorithm was validated against the gold standard of human review in 1143 abstracts and yielded a sensitivity of 97% and a specificity of 100% for identifying cancer abstracts and an accuracy of 95% for identifying cancer site. Using NCI’s SEER database, site-specific mortality to incidence ratios were calculated and multiplied by person-years of life lost to derive cancer-specific lethality for 19 cancer sites. An article proportion for each cancer site was calculated. Article proportion was divided by lethality to calculate Article to Lethality scores for gynecologic malignancies and compared to the other cancer sites. Results: We identified 128,377 articles; 31,045 (24%) were about cancer and 1,189 (3.8%) were about gynecologic cancers. Ovarian, uterine, and cervical cancers ranked 12 th (score 21.9), 13 th (20.9), and 18 th (10.1) out of 19 cancers for median Article to Lethality scores. The highest scores were for breast cancer (score 427) and prostate cancer (234). Ovarian and uterine cancers had lower Article to Lethality scores compared to 11 other cancers, while cervical cancer was lower than 16 other cancers (p &lt; 0.01 for all comparisons). Analyses of the trends for gynecologic cancers over the last 18 years showed no change in Article to Lethality scores. Conclusions: Article to Lethality scores for gynecologic cancers are significantly lower than other cancer sites, indicating a disparity in research publications in high impact factor journals that persists over the last 18 years. Increased funding is essential to ensure continued advancement and progress in research for women with gynecologic cancers.[Table: see text]
Safety and efficacy of allogeneic CAR-T cells in B-cell malignancies: A systematic review and meta-analysis.
Authors: Asmi Chattaraj, Mohammad Ebad Ur Rehman, Israr Khan, Diana Franco, Atif Ibrahim, Razwana Khanam, Nayha Tahir, Qamar Iqbal, Syed Hamza Bin Waqar, Pranali Santhoshini Pachika, Rafiullah Khan, Faiz Anwer
Journal: Journal of Clinical Oncology (2022)

e19530 Background: Immunotherapy with chimeric antigen receptor T (CAR-T) cells has proven effective in recent trials for patients with B cell malignancies, who relapsed after stem cell transplantation. Genetically modified allogeneic CAR T-cells used in advanced B cell malignancy engage with multiple target allo-antigens along with CD19 and/or CD20, leading to elimination of malignant B cells resulting in a potent graft versus malignancy effect with avoidance of tumor escape. Some concerns regarding their use exist like life-threatening graft-versus-host disease (GVHD) and rapid clearance by the host immune system. This study summarises the efficacy and safety of allogeneic CAR-T therapy in B cell malignancies. Methods: A systematic literature search was conducted on PubMed, Embase, Cochrane and Clinicaltrials.gov from inception to Jan 26, 2022, using MeSH terms and keywords for B cell malignancies and CAR-T therapy. We also screened the data presented in various conferences and handpicked references from previous systematic reviews. Outcomes of interest were complete remission (CR), 1-year overall survival (OS), GVHD, cytokine release syndrome (CRS), and immune effector cell associated neurotoxicity (ICANS). Proportional outcomes were pooled using a random effects model (Freeman-Tukey double arcsine transformation) in OpenMetaAnalyst software. Results: The initial search retrieved 1247 articles. After excluding reviews, duplicates and non-relevant articles, we included data from 9 clinical trials (n = 146 patients). The most common malignancy was acute lymphoblastic leukemia (125 patients, 86%). The median age of patients ranged from 19 to 49 years. All patients received CD19 targeting therapy and the cell dose administered ranged from 0.4×10^6 to 5×10^8 cells/kg. CR was reported in 93 of 146 patients, with a pooled rate of 63% (95% CI 47.4 - 78.6%; I 2 78.5%). The pooled 1-year OS was 57.3% (95% CI 30.8 - 82%; I 2 79.2%). The pooled proportion of GVHD was 9.4% (95% CI 3.1- 15.6%; I 2 47.6%). The pooled CRS and ICANS rates were 59.3% (95% CI 30.5 - 88.1%; I 2 95.2%) and 15.4% (95% CI 4.6 - 26.3%; I 2 72.7%), respectively. Conclusions: Allogeneic CAR-T therapy has demonstrated acceptable efficacy and safety in B cell malignancies, with CR being reported in about 60% of patients and GVHD in &lt; 10% of patients. Although allogeneic CAR-T cells are showing promise, several trials are ongoing and we need longer follow up.[Table: see text]
A multicenter real-world study of tumor-derived DNA from cerebrospinal fluid in genomic profiling of NSCLC with central nervous system metastases.
Authors: Yongping Mu, Wei Guo, Xia Zhang, Kai Wang, Mingming Yuan, Rongrong Chen, Jun Bai, Qun Hu
Journal: Journal of Clinical Oncology (2022)

9087 Background: Genomic profiling of cerebrospinal fluid (CSF) could be used to detect actionable mutations to guide the clinical treatment of NSCLC patients with central nervous system (CNS) metastases. Examining the performance of CSF samples in a real-world setting can further confirms the potential of CSF in genotyping for guiding therapy in clinical practice. Methods: A total of 1097 samples were collected from 773 treated NSCLC patients with CNS metastases in a real-world setting, including 117(10.67%) CSF samples, 287(26.16%) tissue samples and 693(63.17%) plasma samples. All samples were subjected to the targeted next-generation sequencing of 1021 cancer-relevant genes. Results: Of these 1097 treated samples, somatic alterations were identified in 112 (95.72%) of the CSF samples, comparing with 287 (100%) of tumor tissue samples and 592 (85.43%) of plasma. Among the tumor tissue samples, 242 were non-intracranial tissues, which could not reveal the unique genetic profiles of intracranial metastases. The median of maximal somatic allele frequency of CSF samples (72.35%) was significantly higher than those of plasma (1.30%) and tumor tissues (37.30%) (all p&lt;0.001). In the thirty-two pairs CSF and plasma samples tested simultaneously, 442 alterations were detected, of which 377 were detected in CSFs and 92 in plasma. 27 alterations could be detected in both plasma and CSF, 65 were not detected in CSFs and 350 were not in plasma, the same alterations were 10.91% (27/442). For SNV or InDel, 220 mutations were detected, of which 155 were detected in CSFs and 89 in plasma, the same mutations were 10.91% (24/220). For CNVs, 216 CNV alterations were detected, of which 216 were detected in CSFs and only one in plasma. We compared actionable mutation of these 1097 treated samples to further analyze the detection capability of actionable mutations of CSF samples in this real-world setting (Table). Compared with plasma, the detection rates of all actionable mutation and actionable EGFR in CSF were significantly higher than those in plasma samples (93.16% vs. 53.97% for all actionable mutation, 83.76% vs. 39.54% for EGFR, all p&lt;0.001).Conclusions: This real-world large cohort study verified that CSF had higher sensitivity than plasma for identifying actionable mutations. In the process of multiple comparison, it can be seen that CSF is better than plasma in detecting alterations, especially in detecting CNV alteration. CSF can be used as a substitute in genomic profiling for NSCLC patients with CNS metastases when there is no intracranial tumor tissue.[Table: see text]
Update results from ALTER-H004 study: Anlotinib combined with TACE as adjuvant therapy in hepatocellular carcinoma patients at high risk of recurrence after surgery—A single-arm, multicenter, phase II clinical trial.
Authors: Zheng Wu, Zheng Wang, Lei Zhang, Xiaojing Song, Xilin Du, Kai Tan
Journal: Journal of Clinical Oncology (2022)

e16120 Background: Hepatectomy is considered to be an effective curative treatment for hepatocellular carcinoma (HCC), however, high recurrence rate after curative resection severely reduces the long-term survival of HCC patients (pts). Transarterial chemoembolization (TACE) as adjuvant therapy has been proved to improve clinical outcomes for pts with high recurrence risk factors after hepatectomy, but the effect is still unsatisfactory. ALTER-H004 trial was designed to evaluate the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. Here we updated the results at the data cutoff of January 20, 2022. Methods: This single arm, multicenter, phase II trial of ALTER-H004 was planned to enroll 30 pts which with histologically confirmed HCC and undertook hepatectomy within 1-2 months. The recruited pts who did not recieve any previous tumor-related treatment must have any of the following high risk factors: ≥5 cm and &lt; 10 cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng's classification I/II). Eligible pts received conventional TACE treatment within 1-2 months after hepatectomy. On the 3-5th day after TACE treatment, oral anlotinib (12mg, qd, d1-d14, q3w) was given until disease recurrence or unacceptable toxicity. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: By the cutoff date of January 20, 2022, 26 pts were enrolled and 25 pts received at least once tumor assessment. According to RECIST 1.1, 14 of 25 did not progress were still on treatment and 7 relapsed. One withdrew the consent and 3 discontinued because of intolerable adverse events. The longest duration of treatment is 16.53 months. The DFS were not mature and the 6-month DFS rates were 77.45% (95% CI: 53.83̃89.99). 12 of 25 pts (48.0%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 5 pts (20.0%) included hypertension (8.0%), leukocytopenia (8.0%) and ascites (4.0%). No grade 4 or 5 TRAEs occurred. Conclusions: The update results suggested that anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited promising clinical benefit and favorable safety profile, and the results needed to be confirmed in trials continued subsequently. Clinical trial information: NCT04213118.
Practice of antibiotic prophylaxis in patients undergoing mastectomy without immediate reconstruction: A survey of breast surgeons in Pakistan.
Authors: Russell Seth Martins, Hania Shahzad, Taleaa Masroor, Abida Khalil Sattar
Journal: Journal of Clinical Oncology (2022)

e13519 Background: Incidence of surgical site infections after breast surgery range from 0.8-26%. Though preoperative antibiotic prophylaxis (AP) is widely used, international and national guidelines lack focus on post-operative antibiotic prophylaxis (PAP). This survey of surgeons in Pakistan reports surgeon preference for AP in cases of mastectomy without immediate reconstruction but with indwelling drains. Methods: An anonymous, online, validated 16-item survey, exploring peri-operative antibiotic choices and prescribing practices was disseminated to a working-group of 30 leading breast surgeons in Pakistan. Descriptive statistics were performed using Statistical Package for Social Sciences (SPSS) version 21. Results: A total of 25 (response rate: 83.3%) members responded, with the majority being fellowship-trained breast surgeons/surgical oncologists (68%) and having &gt; 10 years’ experience (60%). For mastectomy without reconstruction, though most (76%) reported routine use of pre-operative AP, there was considerable variation in post-operative AP. 36% reported no further AP after a single dose of pre-operative AP, 24% continued AP for 24 hours in high-risk patients only, while 24% continued AP for 24 hours in all patients. 12% continued post-operative AP in all patients for 7 days, while 4% reported continuing post-operative AP for the duration of indwelling drains. Antibiotic choice for peri-operative AP also varied. 56% used cephalosporins, 24% used penicillin, and the remaining 20% reported that their choice varied across patients. Conclusions: There is widespread variation in surgeon comfort with discontinuation of AP after the first pre-operative dose in patients undergoing mastectomy without immediate reconstruction but with indwelling drains. Large randomized controlled trials are necessary to develop guidelines to ensure uniformity and evidence-based post-operative AP.
A comparison of invasive squamous cell carcinoma greater than 1 year after treatment with 5-fluorouracil, imiquimod, or photodynamic therapy with aminolevulinic acid
Authors: Brian Cheng, Surya Veerabagu, Christopher J. Miller, Joseph F. Sobanko, Thuzar M. Shin, H. William Higgins, Cerrene N. Giordano, Jeremy R. Etzkorn
Journal: Journal of the American Academy of Dermatology (2022)
RARE-09. Treatment of childhood-onset craniopharyngioma patients using proton beam therapy versus photon-based radiation therapy in the prospective KRANIOPHARYNGEOM 2007 trial
Authors: Carsten Friedrich, Svenja Boekhoff, Panjarat Sowithayasakul, Maria Eveslage, Brigitte Bison, Beate Timmermann, Hermann L Müller
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Proton beam therapy (PBT) compared to photon-based radiotherapy (XRT) offers the benefit to administer lower radiation doses to critical organs thereby possibly minimizing the risk of sequelae in patients with residual craniopharyngiomas (CP) after hypothalamus-sparing surgery. The validation in large CP patient cohorts is still pending. PATIENTS AND METHODS: Of 290 childhood-onset CP patients included 2007-2019 in the prospective multicenter trial KRANIOPHARYNGEOM 2007, 99 (34%) received external RT (65% PBT, 35% XRT). Outcome was compared between the different groups in terms of overall (OS) and event-free survival (EFS), quality of life (QoL using PEDQOL), functional capacity (FMH), and auxological data (BMI and height SDS) one, three and five years after irradiation/CP diagnosis. RESULTS: PBT became the predominant irradiation technique during the study period (used in 23% and 77% of all irradiated patients registered within the first and second half of the enrollment period, respectively). PBT as well as XRT were associated with high (p&amp;lt;0.001) EFS (PBT: 0.917 ± 0.040; XRT: 0.940 ± 0.041) compared to non-RT (EFS: 0.669 ± 0.044). OS was similar in all groups. No differences between PBT, XRT and non-RT CP patients concerning functional capacity and anthropometric parameters (height SDS, BMI SDS) have been obtained. Only in the PEDQOL domain “physical function”, proxy-assessed QoL was lower one year after PBT when compared to XRT treated and non-irradiated CP patients. CONCLUSION: PBT is similar efficient in preventing relapses and recurrences in childhood-onset CP patients. During follow-up, no clinically relevant differences between PBT and XRT in terms of QoL, functional capacity and degree of obesity as a marker of hypothalamic syndrome were detectable. While PBT is increasingly applied, studies on larger CP cohorts with longer follow-up after RT are warranted to analyze, whether it can prevent sequelae such as hypothalamic syndrome and severe obesity compared to XRT.